Correlation of Dose Intensity and Prognosis in Adjuvant Chemotherapy: An Extended Controversy

Abstract

In animal model systems, the outcome of chemotherapy depends upon drug dose, tumor sensitivity, and tumor burden. In animals, optimum treatment can be determined by treating beyond lethal toxicity. This is not possible in humans, where attempts to define optimum treatment have resulted in many schedules and combinations, and attempts to avoid serious toxicity have produced many schemes to reduce doses and delay treatment. However, these schedules and schemes have obscured dose-response relationships and have led to confusion. Dose-response relationships can be rediscovered and the confusion can be cleared by expressing all treatments in terms of how much drug is given per unit time. This is dose intensity (Green and Dawson 1980). Dose intensity may be calculated from intended drug doses (“projected dose intensity”) or from doses received after reductions and delays because of toxicity (“received dose intenstiy”) (Hryniuk and Bush 1984).